Extended release pharmaceutical compositions of levetiracetam
Inventors
Gallagher, Michela • Rosenzweig-Lipson, Sharon • Melsopp, Elsie • James, Jack Lawrence
Assignees
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Publication Number
US-10925834-B2
Publication Date
2021-02-23
Expiration Date
Abstract
This invention relates to novel extended release pharmaceutical compositions of levetiracetam and preparations and characterizations thereof. This invention further relates to using these extended release pharmaceutical compositions of levetiracetam for the treatment of cognitive impairment associated with central nervous system (CNS) disorders in a subject in need or at risk thereof.
Core Innovation
The disclosed invention provides an extended release pharmaceutical composition comprising levetiracetam. The composition provides a steady state plasma concentration of levetiracetam in a subject within a defined time window after administration and is extended for a defined duration during a 24-hour period. The disclosure includes once daily dosing and is directed to treating or improving cognitive impairment associated with central nervous system (CNS) disorders.
The problem addressed is cognitive impairment associated with CNS disorders, including age-related cognitive impairment and mild cognitive impairment, including Alzheimer’s disease-related mild cognitive impairment and amnestic mild cognitive impairment (aMCI). The document targets cognitive outcomes and provides a pharmacokinetic framework for maintaining levetiracetam exposure within specified plasma concentration ranges over an extended portion of a 24-hour period.
The disclosure further includes composition formulation discussion for levetiracetam extended release tablets, including strengths and excipients such as hypromellose, colloidal silicon dioxide, silicified microcrystalline cellulose, and magnesium stearate, with optional alternatives such as anhydrous dicalcium phosphate. The document also describes dissolution testing and pharmacokinetic comparisons and a human Phase I food-effect study with steady-state PK modeling tied to target plasma level goals.
Claims Coverage
The provided independent claims define an extended release levetiracetam composition by two quantitative inventive features: a steady state plasma concentration range (1.9 μg/ml to 4.4 μg/ml) and timed achievement/maintenance constraints over a 24-hour period.
Extended-release levetiracetam steady state window and achievement within 3 hours
An extended release pharmaceutical composition comprising levetiracetam, wherein the composition provides a steady state plasma concentration of levetiracetam in a subject of between 1.9 μg/ml and 4.4 μg/ml within 3 hours after administration and extending for at least 8 hours of a 24-hour period after said administration.
Extended-release levetiracetam steady state window and achievement within 1 hour with longer maintenance
An extended release pharmaceutical composition comprising levetiracetam, wherein the composition provides a steady state plasma concentration of levetiracetam in a subject of between 1.9 μg/ml and 4.4 μg/ml within 1 hour after administration and extending for at least 13 to 16 hours of a 24 hour period after said administration.
Across the independent claims, the inventive concept is maintaining levetiracetam steady state plasma concentrations between 1.9 μg/ml and 4.4 μg/ml, with different requirements for how quickly the range is reached after administration and how long it is maintained during a 24-hour period.
Stated Advantages
Once daily dosing.
Maintaining levetiracetam exposure within specified plasma concentration ranges over an extended portion of a 24-hour period.
Documented Applications
Treating or improving cognitive impairment associated with CNS disorders, including age-related cognitive impairment/mild cognitive impairment and Alzheimer’s disease-related mild cognitive impairment (including amnestic mild cognitive impairment (aMCI)).
Treating mild cognitive impairment due to Alzheimer’s disease in a human subject by administering the pharmaceutical composition.
Slowing the progression of mild cognitive impairment due to Alzheimer’s disease in a human subject by administering the pharmaceutical composition.
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